IJPCBS 2016, 6(4), 385-394 Elizabeth Margaret et al. ISSN: 2249-9504

INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES

Available online at www.ijpcbs.com Review Article

THERAPEUTIC PROPERTIES OF JATIPAL - FRAGRANCE. HOUTT

PV. Neeraja and Elizabeth Margaret* Department of , Ann’s College for Women, Mehdipatnam, Hyderabad-500 028, Telangana, India.

A B S T R A C T Myristica fragrans Houtt, traditionally known as Jatiphal and Javitri in India, belongs to the family th is known for its flavour and therapeutic action since 18 centaury in alternative medicinal systems. It is a good body detoxifier, stimulates the brain. Ethanol extract shows antifungal, spasmolytic, carminative, hepatoprotective, antiviral, anticarcinogenic, antioxidant, antimicrobial properties. Nutritionally, is rich in energy, carbohydrates, proteins and dietary fibre. Seed is a rich source of vitamins. It also contains electrolytes minerals and phytonutrients including carotene-B and crypo-xanthin . Myristica fragrans has a lot of industrial applications in liqueurs, soap production and cosmetics. This review article elucidates the information regarding the phytochemistry and pharmacological activity of the which provides the basis for further research.

Keywords: Myristica, Myristicin, Detoxifier, Jatiphala, Nutmeg.

INTRODUCTION terpenoids, alkaloids, flavonoids, lignans and Nutmeg (Myristica fragrans) Houtt (Family: phenolics, etc. These compounds render their Myristicaceae), an aromatic plant whose seed is effects via different mechanisms such as radical widely used as a spice, is a tropical, dioeciously scavenging, metal chelating, and inhibition of evergreen native to the Moluccas or Spice lipid peroxidation and quenching of singlet Island of , in India it is found mostly in oxygen to act as antioxidants. Tamil Nadu and to some extent in Kerala, Nutmeg is used to flavour many kinds of baked Andhra Pradesh and Assam. Nutmeg has a goods, confections, puddings, meats, sausages, characteristic pleasant fragrance and is slightly saucers, vegetables, and beverages warm taste, mostly related to various activities (Panayotopoulos and Chisholm, 1970). It is also of their essential oils, such as antimicrobial, used as components of curry powder, teas and antioxidant, antifungal spasmolytic, carminative, soft drinks, or mixed in milk and alcohol. hepatoprotective, antiviral, anticarcinogenic The herbal drug yields two kinds of oils i.e., the (O.A. Olajide, F.F.1999) (Tajuddin, et.al 2003), compressed fatty oil and the steam distilled memory enhancer, antidiarrheal (J.K. Grover, S. essential oil. Khandkar et.al.,2002), anti inflammatory etc. It Because of the inhibition of prostaglandin is found effective as a stimulant, carminative as synthesis in the mucosa and sub mucosa of the well as for intestinal catarrh and colic. It colon it is used as anti-diarrheal agent for the stimulates appetite, control flatulence, and has a patients with medullar carcinoma of thyroid. reputation as an emmenagogue (to promote and regulate menstrual flow) and abortifacient The Genus (Green, 1959; Panayotopoulos and Chisholm, There are 150 species of Myristica 1970). It is used in alternative medicine as it has been Common Names(s) reported to have a variety of active Sanskrit: Jatiphala,Jaiphol , Telugu: Jjajikaya phytochemicals including vitamins, carotenoids, Bengali: Jatiphala, Jayaphala,Gujarati:

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Jayaphala,Hindi: Jati-phal, Jayaphal Kannada: while male flowers contain fused . Jakayi, Malayalam: Jathikka, Marathi: Jatiphala, Fruits yellow, broadly pyriform or globose, Nepali: Jaiphal, Oriya: Jasiphala,Punjabi: fleshy pericarp, split into two equal halves when Jafal,Tamil: cati-k-kay. mature. Seed ellipsoid, 20-30 mm long and Distribution about 20 mm broad, brown with a dark points Myristica species are cosmopolitan in and lines slightly furrowed reticulately distribution but abundant in Moluccas and indicating the position of the radical a groove Banda Islands in the South Pacific. Tropical running along the line of raphe to the darker regions, like Indonesia, in the West chalaza of embryo. Indies and Sri Lanka cultivate nutmeg. Pollinator: Formicomus braminus (Beetle) (Purseglove, 1968; Bown, 1995). Five species Useful part: Seeds (nutmeg) and aril (mace). are found in South India (Gamble, 1921). M. dactyloides Gaert. is reported in the W. Ghats of Nutritional Value Tamil Nadu (Mathew, 1999;Henry et.al;1987) Nutmeg is a rich source of vitamins (Vit. A, C. and E), electrolytes (Sodium and Potassium) Systemic Position minerals (calcium, copper, iron, magnesium, Plantae manganese, zinc and Phosphorus), Angiosperms phytonutrients( carotene-B and crypo-xanthin B) , moisture (14.3%) either extract (36.4%), fibre (11.6%) volatite oil(6-16%), starch (4.6- Myristicaceae 24.24.2%), pentosans (2.25%), furtural (1.5%) Myristica and pectin (0.6%) (Gordon, 2005).

Morphology of the Plant Anatomy of Fruit The South Indian species of Myristica are Pericarp (Fruit Wall) identified on the basis of inflorescence, leaf It is reported to be around 7mm thick and three venation, fruit shape and colour of the aril. layers( N.Parimala1 & S.Amerjothy 2013). Myrstica fragrans is moderate sized evergreen Epidermis- It is considered to be the epicarp tree grows up to 25 meters in height. Root is tap and is made up of unistratose and consists of root, Stem is aerial, erect , branched , woody , narrowly oblong thick walled cells with Leaves are elliptic or oblong – lanceolate, shiny prominent cuticle. Hypodermis- Tangentially above and dull beneath with reticulate venation. stretched parenchymatous cells are present in Inflorescence is Flowers creamy yellow, this zone. Sclereid Zone – A discontinuous zone fragrant, and unisexual. Perianth is fused into an made up of brachysclereids. urn-shaped enclosure. The female flowers are Mesocarp- Composed of multilayered small, with one pistil containing a single ovule parenchymatous, polyhedral cells.

Twig bearing Fruits Inflorescence L.S. of Male Flower

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L.S of Fruit with Seed & Aril Dried Aril Seeds

Buds Pollen on Anther L.S of Male & Female Flower

Vascular Bundles- Small vascular strands are ruminated endosperm this is made up of soft found scattered in the mesocarp found in parenchymatous cells. clusters of three, they are collateral and Is flat, ribbon like repeatedly lobed creamy conjoint, xylem with angular thickening and when young and dark red when matured and prominent phloem. easily separable from the seed. It is 400μm thick in the middle and 150μm thick at the ends. Anatomy of Seed Epidermis- The epidermal cells are 10μm thick. It has 140 μm in thick seed coat Cortex - The ground tissue of the aril is in Epicarp (Seed Coat) admixture of small and larger cells. The larger Outer layer of cells are small, squarish and inner cells are oil bearing idioblasts. They are angular layer of the cells made up of radially elongated in outline and fairly thick walled. The idioblasts palisade like cells, this layers also shows the are 40μm wide, presence of tannin cells. in between the idioblasts are smaller, angular or Vascular Bundles-Vascular Bundles are spindle shaped parenchyma cells. scattered in inner layers. Vascular Bundles-In the median part of the aril Perisperm-Differentiated in three layers there are prominent discrete vascular bundles Outer zone- It is 450-500µm thick and consist of arranged in a plate. The vascular bundles have angular parenchymatous cells and Calcium small, strands of phloem and xylem elements Oxalate crystals. Middle zone- Made up of radial elongated row of Anatomy of Mace (aril) cells. The aril is 400µm thick in the middle and 150µm Inner zone- Cells with dark amorphous cells thick at the ends, differentiated in to with variable shapes and sizes. Many elongated parenchymatous epidermis, parenchymatous thread like cells that are 2mm long and 450µm cortex with idioblasts (40µ wide) and in the made up of spongy parenchyma cells these centre lie prominent discrete vascular bundles.( threads in the interior show well developed N.Parimala1 & S. Amerjothy 2013) collateral vascular bundles. Phytochemistry of Seed Endosperm The chemical composition of the acetone extract Young Endosperm- Occupies maximum portion of nutmeg seed said to contain 32 different of the seed. compounds representing 99.49% of the total Matured Endosperm- Due to the intrusion of extract (Ashish Deep Gupta 2013). Sabinene perisperm many radial lobes are formed called (28.61%), b-pinene (10.26%), apinene (9.72%)

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(G.R. Mallavarapu 1998). Other important Phytochemistry of Mace compounds are terpinen-4-ol (5.80%), The oil of mace contains the same aromatic myristicin (4.30%), limonene (3.76%), c- component as that of seed but in slightly terpinene (3.71%), (Z)-p-menth-2-en-1-ol different amounts and flavour. Apart from (3.21%), isoeugenol (2.72%), elemicin (2.67%), monoterpene hydrocarbons, p-dimethylstyrene (E)-p-menth-2-en-1-ol (2.15%), myrcene has been identified along with seven esters, (2.14%), a-phellandrene (1.84%),p-cymene eight sesquiterpene hydrocarbons and two (1.81%), terpinolene (1.63%) and linalool unsaturated aliphatic compounds namely 3- (1.12%).Difference in the chemical composition methyl -4-decan-l-ol and its acetate ( Schenk & of the nutmeg has been reported which could be Lamparsky 1981).Red colour of the mace is an attribute of difference in climate, cultivar, soil identified to lycopene (Gopalakrishnan 1979) factor and solvent used for the extraction (G.R. neolignans,fragnasol C and D and myristicanol A Mallavarapu 1998). and D have been reported (Rastogi & Mehrotra 1995; Miyasawa et al 1996).

Myristicin Methyl Eugenol Trimyristicin

Estragole Methy Iso Eugenol Iso Eugenol

Dillapiole Anethole Saforole

Eusarone αAsarone Elemicin

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Essential oils of Seed acids (Tan KP et al 2013),caffic acid and catechin The percentage phytochemical compounds (Shan B2005)(Gowri Pendyalan et al.,2008) present in seed essential oil are Thujene 0.78, Pinene 10.23, Camphene 0.16, Sabinene Aphrodisiac 21.38,Myrcena 2.38,Terpinene 2.72, Limonene Since 18th century, the spice is being used to 5.57,Ocimene 0.03,Terpinene 3.98, Trans- treat male sexual dysfunctions it is clinically Sabinene Hydrate 0.03, Terpinolene 1.62, proved by Orabi et al., 2000 (Tajuddin et al. Linalool 0.75, Fenchyl Alcohol 0.05, Cis-Sabinene 2005). Hydrate 0.06, 4-Terpineol 13.92,Terpineol 3.11, Citronellol 0.77, Linalyl Acetate 0.06, Bornyl Anti-inflammatory Acetate 0.24, Safrole 4.28, Methyl Eugeunol 0.77, Triglyceride Trimyristin of nutmeg oil shows Isoeugeunol 1.74, Myristicin 13.57, Elimicin anti-inflammatory properties and is used as 1.42, Metoxyeugeunol 0.10,Asaron 0.03, Myristic local message to reduce muscular pain and Acid 0.11, Ethyl Miristate 0.04, Palmitic Acid rheumatic pain of joints (Pamphona-Roger, 0.03, Ethyl Palmitate 0.07, Stearic Acid 0.01, 1999).It reduces joint swelling and treats Ethyl Oleate 0.01(Muchtaridi et.al. 2010) and rheumatic fever (Duke and Edward, 1985; triglyceride Trimyristin that has anxiogenic Ernest, 2002). activity and is used in polyherbal formulations. Antidiabetic activity Pharmacological Properties Macelignan present in the seeds enhanced the Antiangiogenic Activity insulin sensitivity and improved lipid metabolic Compounds like myristicin, limonene, eugenol disorders by activating peroxisome proliferator and terpinen-4-ol of nutmeg essential oil receptor and attenuating endoplasmic reticulum attribute antiangiogenic activity. Myristicin have stress, suggesting that it is an ant diabetic agent been reported to induce cytotoxicity in human for the treatment of type 2 diabetes (Han et al., neuroblastoma SK-N-SH cells by mean of 2008). apoptotic mechanism (Lee BK et.al., 2005). D- limonene is a chemo preventive agent in Dental Care hepatocellular carcinoma models(Parija T et.al., Eugenol of nutmeg relieves from toothache 2000., DK Patel et.al 2010 and terpinen-4-ol and (Duke et al., 2002; Kokwaro 2009), prevents bad Eugenol showed that they can induce apoptosis breath (Barceloux, 2009) in human melanoma cells(Calcabrini A et al., 2004) (Hussain A et.al 2009). Memory enhancing activity Parle et al. (2004) have investigated the effect of Antimicrobial M. fragrans seeds on learning capabilities and Extracts of nutmeg showed antimicrobial memory level in mice. Administration of the n- activity against gram positive (Bacillus subtilis hexane extract of M. fragrans at the lowest dose and S. aureus) Orabi et al., 1991; De et al., 1999; of 5 mg/kg body weight for 3 successive days Dorman & Deans, 2000, gram negative significantly improved the learning and memory (Pseudomonas putida and P. aeruginosa) level of young and aged mice. The extract said to bacteria and pathogenic fungi (Aspergillus have reversed scopolamine and diazepam- fumigatus, A. niger and A. flavus) .Ethanol extract induced impairment in learning and memory of of fresh, seed and mace of Myristica fragrans is a young mice. The observed memory enhancing classic remedy for the periodontal diseases that effect of M. fragrans may be attributed to a occurs by accumulation of Actinomyces viscosus, variety of properties (individually or in Porphyromonas gingivalis, Streptococcus mutans combination) such as antioxidant, anti- and streptococcus sanguis in the form of an inflammatory, or procholinergic activity. adherent plaque (Zaleha Shafiei et.al 2012) these properties are attributed by myristin and Digestive triglyceride Trimyristin The decoction of the nutmeg is used for the treatment of flatulence, nausea and vomiting Antioxidant (Kurian, 2010).External application of the oil Anti-oxidant properties has been determined by relieves the stomach pain. Freshly prepared the ferric reducing antioxidant power and decoction with honey has been used to relief of trolox equivalent antioxidant capacity (Tan KP nausea, gastritis and indigestion ailment et al 2013). Anti-oxidant property of nutmeg is (Doman et al., 2000). contributed by various phytochemicals, mainly vitamins, carotenoids, terpenoids, alkaloids, flavonoids, lignans, simple phenols and phenolic

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Piles relieving formation of DNA adducts by aflatoxinin vitro Piles are cured by applying nutmeg past mixed (Hashim et al. 1994). The dihydroguaiaretic acid with Vaseline. from M. fragrans mace suppressed leukaemic cells, colon cancer and lung cancer cells in vitro Heart Functioning (Park et al. 1998). The mace of M. fragrans Nutmeg proves to be an excellent tonic for the protected from bone marrow genotoxicity in cardiovascular system. It increases the blood male Swiss albino mice (Kumari 1992). It also circulation and stimulates the heart functions significantly protected from (Balick and Paul, 2000). methylcholanthrene-induced carcinogenesis in uterine cervix of mice (Hussain & Rao 1991) and Antifungal had chemo preventive effects on dimethylbenz Essential oils of nut meg posses antifungal anthracene (DMBA)-induced papillo-magenesis properties against Colletotrichum in the skin of mouse (Jannu et al. 1991). gloeosporoides, Colletotrichum musae, Fusarium oxysporum , Fusarium semitectum , Aspergillus Jaiphal for pimple niger and Aspergillus glaucus (V. Pooja et.al A paste of nutmeg made with water or milk is .,2012) applied externally to treat pimple and acne scar. Ground nutmeg powder made into a paste with Spasmolytic Sandalwood, Kumkumadi taila, olive oil etc can Nutmeg is helpful in clearing up the congestion be used for face resulting from cold and thus, is widely used in cough syrups. It’s even helpful in aroma therapy Weedicidal (Gill, 1992; Iwu, 1993). The essential oil, obtained from the leaves is Carminative toxic to weeds hence used as weedicides, could Nutmeg is said have good carminative also be use in the preparation of chewing gums properties(Seenivasan et.al.,2006) and other flavouring essences (Pandey, 2005).

Hepatoprotective Pesticidal properties Morita et al. (2003) have reported that The aqueous decoction of seed is toxic to myristicin from M. fragrans (nutmeg) possessed cockroaches (Krishnamurthy et al. 2001). most potent hepatoprotective activity to rats Nematicidal activity of M. Fragrans seed against with liver damage induced by Meloidogyne incognita has been reported (Gotke lipopolysaccharide (LPS) plus D-galactosamine & Maheswari 1990). (D-GalN). It was reported that myristicin markedly suppressed LPS/D-GalN-induced Insecticidal enhancement of serum TNF-alpha Jung et al. (2007) have reported the insecticidal concentrations and hepatic DNA fragmentation properties of M. fragrans seed compounds in mice. These findings suggest that the against adult females of Blattella germanica hepatoprotective activity of myristicin may be, (Dictyoptera: Blattellidae). Myristicin present in at least in part, due to the inhibition of TNF- the kernel may be employed as an additive to alpha release from macrophages. Sohn et al. pyrethrum to enhance the toxicity of the latter (2008) observed that the hepatoprotective to houseflies, although myristicin itself is effects of macelignan, isolated from M. fragrans inactive (Anonymous, 1995). The aqueous is related to activation of the mitogen activated decoctions of M. fragrans have been found to be protein kinase (MAPK) signaling pathway, toxic to cockroaches (Anonymous, 1995). especially JNK and c-Jun. Essential oil of M. fragrans has insecticidal activity against larvae of Lycoriella ingenua Insomnia (Park et al., 2008) and Callosobruchus chinensis Nutmeg seeds increase the levels of serotonin (Chaubey, 2008). that brings the relaxation of the body.(Pandey, 2005). Adverse effects and Toxicity No evident of adverse physiological or Anticarcinogenic neurological is said to reported when used in Extracts of nutmeg suppressed the growth of minimum but large doses of raw nutmeg has human lymphoid leukaemic cells, Molt 4 B psychoactive effects due the presence of (Moteki et al. 2002). Myristicin, present in the myristicin, a monoamine oxidase inhibitor and volatile oil of M. fragrans is a potential cancer psychoactive substance (Helena Hallstrom et.al chemo preventive agent (Zheng et al.1992). The 1997). Myristicin poisoning can induce essential oil is reported to modulate the convulsions, palpitations, nausea, eventual

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dehydration, and generalized body pain umbilical cord for early drying. (M. Hamambara (Demetriades, AK et.al 2005). In human beings Reddy.et.al., 2000) 6-7 mg/kg body weight of nutmeg is enough to The Nag clan of the Rai Ghatual tribe residents cause psycho pharmacological effects. 1-2 mg of Tanki Tila village in Moulvibazar district of myristicin/ kg body weight obtained from 5gm Bangladesh use leaves of Andrographis of seeds causes intoxication (Helena Hallstrom paniculata , Ocimum tenuiiflorum and Justicia 1997). Prostaglandin production is inhibited by adhatoda along with seeds of Myristica fragrans Myristica extract that leads to hallucinogens that and Nigella sativa to treat of fever and loss of may affect the foetus if consumed in large appetite. The plant parts are crushed and juice quantities (Herb and drug safety chart Herb and obtained made in to pills administered orally.( drug safety chart from Baby Centre UK ). Protiva Rani Das.et.al.,2013) Toxicological effects including weak pulse, Nandurbar tribes of Maharastra district use hypothermia, delirium, vertigo and nausea decoction of nutmeg seeds for vomiting and associated with ingestion of M. fragrans has hiccups. (S. K. Tayade. et. D. A. Patil 2010). been reported (Hallstrom & Thuvander 1997). Zaki & El (1987) reported teratogenic effects of Conservation Status nutmeg in foetus of rats. Randerath et al. (1993) International Union for Conservation of Nature reported the development of covalent and Natural Resources Red List-2015 of DNA adducts in the liver of adult and foetal mice, Threatened Species 1998: e.T33986A9820569 treated with extracts of nutmeg or mace or of Myristica fragrance has placed it under the myristicin, the major spice constituent of category & criteria of Data Deficient ver. 2.3 nutmeg. Safrole, a minor constituent of nutmeg also produced DNA adducts in the liver of mice. REFERENCES 1. Anonymous. The Wealth of India. Raw Myristica fragrans in Ayurveda materials. New Delhi: Publications and Sanskrit name-Jaitiphala, Malatiphala Information Directorate, CSIR 1995; Rasa : Katu, Tikta 6(L-M):474-9. Guna : Laghu, Tiksna 2. Balick MJ, Paul AC. 2000. that Virya : Usna heal people: culture of science of Vipaka : Katu ethno botany. Scientific American Karma : Dipana, Library, New York. Grahi,Vrsy,Mukhakledanasaka,Mukhadaurgandh 3. Barceloux DG. 2009. Nutmeg yanasaka,Kaphavatapana Myristica fragrans Houtt. Research Important formulations – Jatiphaladi Curna, Journal of Spices 55 6: 373-379. Dadimavaleha,Nasika Churna, Mrita Sanjivani 4. Callosobruchus chinensis (Coleoptera: Gulika Bruchidae). Oleo Sci 2008; 57:171-9. Therapeutic uses – Atisara , Svasa , Chardi , Kasa 5. Chaubey MK. Fumigant toxicity of , Pinasa , Grahami ,Mukharoga , Sukrameha. essential oils from some common Dose - 0.5 - 1.0 g of the drug in powder form. spices against pulse beetle, 6. Chemistry, antioxidant and Unani Medicine antimicrobial potential of nutmeg Javetri or Bisbasa (Mace ) in Unani therapeutic (Myristica fragrans Houtt)Ashish Deep is used for cardiac diseases (Amraz-e-Qalb), Gupta, Vipin Kumar Bansal, Vikash indigestion (Sue Hazim) and sexual debility Babu , Nishi Maithil Journal of Genetic (Zofe Bah). Engineering and Biotechnology Some formulations with Bisbasa (2013) 11, 25–31. Jawarish Bisbasa - Buroodat Meda (coldness of 7. De M, Krishna De A, Banerjee AB. gastric), Sue Hazm (Dyspepsia), Riyahi Dard Antimicrobial screening of some (Gaseous Pain) Indian spices. Phytother 8. Demetriades, AK, Wallman PD, Chinese Medicine McGuiness A, Gavalas MC. Low Cost, SuHeXiang Wan (SHXW), a polyherbal (15 High Risk: Accidental Nutmeg herbs) Chinese traditional drug administered to Intoxication. Emergency Medicine treat central nervous depression, seizures, Journal 2005;22:223–225. infantile convulsion, stroke. (Jeon S et al., 2011) 9. DK Patel, R Kumar, SK Prasad, S Hemalatha. Pedalium murexLinn Folk Lore Medicine (Pedaliaceae) fruits: a comparative Sugalis tribes of Chittoor and Cuddapah use antioxidant activity of its different warm nutmeg oil to gently press on the

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